Sjogren's Syndrome is an autoimmune systemic illness characterized by xerostomia and xerophthalmia secondary to destructive lymphocytic infiltration of salivary and lacrimal glands. The clinical picture runs the spectrum from localized glandular secretory insufficiency a generalized lymphoproliferative disorder at times terminating into lymphoma. Patients present initially to a dentist or otolaryngologist because of rampant dental caries, severe dry mouth or parotid gland swelling. The UTHSC in San Antonio proposes a detailed study of oral health and immune status in patients suffering from SS and is acknowledged international authority in autoimmune disorders. He has assembled a team of dental and medical scientist utilizing the latest techniques of molecular medicine and immunopathology, organized into three projects and two cores. Project I, (Bacteriologic and immunologic Studies of Xerostomia in SS) focuses on the relationship between salivary gland pathology, diminished salivary flow, caries formation, periodontitis and mucosal lesions. A detailed study of salivary bacterial flora, cytokines and immunoglobulins will be performed. Project II, (Regulation of Inflammatory Cytokines in SS Salivary Glands) Utilizes PCR to study the mRNA for pro-inflammatory and anti-inflammatory cytokines in relations to the severity of the SS lesion as determined by biopsy and focus score. Preliminary results suggest that TGFbeta may be an important natural immunosuppressive factor preventing the development of SS. Project III, (Suppression of SS in Transgenic Mice by Diet) employees a new transgenic mouse model for SS to evaluate the effect of low calorie restriction on salivary gland lesion and life spans. The PI of this project, Dr. Gabriel Fernandes, is also the Co-Director of the program and an international authority on diet, immune response and aging. These projects are supported by an Immunopathology Core which make immunoquantitative histochemical analysis for immunoglobulins and cytokines available to all investigators. Administrative Core will assure the availability of statistical and secretarial assistance. Our goal is to contribute to the eradication of SS and related diseases by the end of the century.